1. Field of the Invention
The present invention is directed to non-effervescent, orally disintegrating solid pharmaceutical dosage forms comprising progestin and methods of making and using the dosage forms to treat conditions in females in need thereof.
2. Background Art
Emergency contraception is generally understood to mean the application of contraceptive measures to a female after an act of sexual intercourse (postcoitus) or undesired insemination, especially after unprotected sexual intercourse. Emergency contraceptive pills (ECPs) and intrauterine devices (IUDs) are the currently available forms of emergency contraception. These methods act both to prevent ovulation or fertilization and possibly post-fertilization implantation of a blastocyst (embryo).
Currently available ECPs, also known as emergency contraceptives (EC), contain higher doses of the same steroidal compounds (estrogens and progestins, or progestins alone) found in regular or conventional daily oral contraceptive pills. The progestin-only method uses levonorgestrel (a synthetic progestogen) in two doses of 0.75 mg 12 hours apart (e.g., Plan B®) or in a single dose of 1.5 mg within 72 hours of coitus. The combined or Yuzpe regimen uses both ethinyl-estradiol (0.1 mg) and levonorgestrel (0.5 mg) in two doses 12 hours apart within 72 hours of coitus. The mifepristone method uses a large dose of mifepristone, an antiprogestin, either as an ECP or as an abortifacient, depending on whether it is used pre- or post implantation. Emergency contraceptive methods are described in Von Hertzen, H. et al., Lancet, 352:428-432 (1988); Ho, P. C. et al., Human Reproduction, 8(3):389-392 (1993); U.S. Patent Appl. Pub. No. 2005/0032755; WO 2007/000056; and Von Hertzen, H. et al., Lancet, 360:1803-1810 (2002). Additionally, off-label use of high dose(s) of conventional combined or progestin-only oral contraceptive pills are also available for emergency contraception.
Levonorgestrel, a synthetic progestogen, is commonly used in combination with estrogen as a contraceptive and also can be used alone as an emergency contraceptive. Levonorgestrel is also used to treat menstrual disorders, endometriosis and for progesterone replacement therapy.
Pharmaceutical preparations containing levonorgestrel alone and methods of using levonorgestrel alone for emergency contraception are described in U.S. Patent Appl. Pub. No. 2005/0032755. Pharmaceutical preparations containing levonorgestrel alone are described in CN1634077.
Conventional solid dosage forms can be undesirable for treatment of adults who have trouble swallowing such dosage forms. Additionally, a large number of adult patients suffer from dysphagia and have difficulty swallowing such dosage forms. It is also desirable, particularly for emergency contraception, to administer a dosage form having a rapid and consistent onset of action, a high bioavailability, and sustained activity. Rapid onset of action can be achieved by parenteral injection but this is unacceptable to many patients, and can pose challenges outside a clinical setting. Although liquid syrups can be suitable for this purpose, they can be difficult to handle and administer in an accurate dosage. Many active agents are also unstable in liquids over long periods of time. Thus, an orally disintegrating dosage form that disintegrates in the mouth in the absence of water is desirable for its widespread patient acceptance and ease of administration.